Prominent Drugs Research Articles

Glioblastoma Multiforme miRNA based Comprehensive Study to Validate Phytochemicals for Effective Treatment against Deadly Tumour through In Silico Evaluation.

Glioblastoma Multiforme (GBM) is a prevalent and deadly type of primary astrocytoma, constituting over 60% of adult brain tumors, and has a poor prognosis, with a high relapse rate within 7 months of diagnosis. Despite surgical, radiotherapy, and chemotherapy treatments, GBM remains challenging due to resistance. MicroRNA (miRNAs) control gene expression at transcriptional and post-transcriptional levels by targeting their messenger RNA (mRNA), and also contribute to the development of various neoplasms, including GBM. The present study focuses on exploring the miRNAs-based pathogenesis of GBM and evaluating most potential plant-based therapeutic agents with in silico analysis. Gene chips were retrieved from the Gene Expression Omnibus (GEO) database, followed by the Robust- Rank- Aggereg algorithm to determine the Differentially Expressed miRNAs (DEMs). The predicted targets were intersected with the GBM-associated genes, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the overlapping genes was performed. At the same time, five phytochemicals were selected for the Connectivity map (CMap), and the most efficient ones were those that had undergone molecular docking analysis to obtain the potential therapeutic agents. The hsa-miR-10b, hsa-miR-21, and hsa-miR-15b were obtained, and eight genes were found to be associated with glioma pathways; VSIG4, PROCR, PLAT, and ITGB2 were upregulated while, CAMK2B, PDE1A, GABRA1, and KCNJ6 were downregulated. The drugs Resveratrol and Quercetin were identified as the most prominent drugs. These miRNAs-based drugs can be used as a curative agent for the treatment of GBM. However, in vivo, experimental data, and clinical trials are necessary to provide an alternative to conventional GBM cancer chemotherapy.

Alleviation of Tumor Invasion by the Development of Natural Polymerbased Low-risk Chemotherapeutic Systems - review on the Malignant Carcinoma Treatments.

The spread of tumors (48% in men and 51% in women), as well as the protection of malignant tumors by stromal cells and complex blood vessels, pose significant challenges to drug delivery to tumors. Modern chemotherapy, on the other hand, addresses tumor growth suppression by at least 60% through versatile formulation systems and numerous modifications to drug delivery systems. The renewable and naturally occurring polymers present invariably in all living cells form the fundamental foundation for most anticancer drug development. The review aims to discuss in detail the preparations of polysaccharide, lipid, and protein-based drug-loading vehicles for the targeted delivery of prominent anticancer drugs. It also provides an explanation of drug distribution in blood (cumulative releases of nearly 80% drug) and drug accumulation at tumor sites (1-5 mg/kg) due to enhanced permeability and retention (EPR). Specific delivery examples for treating colorectal and breast carcinomas have been presented to distinguish the varied drug administration, bioavailability, and tumor internalization mechanisms between sugar, fatty acid, and amino acid polymers. Current therapy possibilities based on cutting-edge literature are provided, along with drug delivery systems tailored to tumor location and invasive properties. The unique combinations of the three natural polymers provide unparalleled solutions to minimize the toxicity (<20% drug release) of the chemotherapeutic drugs on normal tissues. Moreover, the development of a consolidated drug delivery system has contributed to a substantial reduction (dose reduction from 10.43 μM to 1.9 μM) in the undesirable consequences of higher dosages of chemotherapeutic drugs. The review extensively covers safe chemotherapeutic systems with significant advantages (tumor volume shrinkage of 4T1 cells from 1000 mm3 to 200 mm3) in clinical applications of carcinoma treatments using natural polymers.

In vitro evaluation of ethyl cellulose and polyvinyl pyrrolidone composite nanofibers for transdermal delivery of diclofenac diethylamine

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prominent painkiller and anti-inflammatory drugs with gastrointestinal (GI) adverse effects. Transdermal drug delivery systems (TDDS) could overcome GI adverse effects associated with oral ingestion of NSAIDs as well as maintaining a prolonged release of the drug. The main aim of this study was to prepare and investigate diclofenac diethylamine (DDA) loaded nanofibers made of ethyl cellulose (EC) and polyvinyl pyrrolidone K90 (PVP) using electrospinning. The impact of penetration enhancers such as nerolidol and farnesol on release profiles through cellophane membranes and other characteristics of nanofibers were also investigated. Based on release studies, some formulations were selected for release examination through rate skin using Franz diffusion cells. To gain insight about potential interactions between drug and polymers FTIR, DSC, and XRD analyses were performed. Morphology examination was also conducted using scanning electron microscopy (SEM). Morphology studies showed that nanofibers made of EC only are greater in the mean diameter than other nanofibers while other formulations were not significantly different from each other regardless of the presence of penetration enhancers. EC nanofibers had the lowest elastic modulus and tensile strength and most elongation at break which makes them the least tough and most flexible nanofibers among all the formulations. The addition of PVP increased the toughness and decreased the flexibility of nanofibers. The addition of nerolidol did not alter the mechanical properties of nanofibers significantly, while the addition of farnesol increased elastic modulus, tensile strength, and elongation at break significantly in a concentration-dependent manner. EC nanofibers had the lowest release rate and lowest total cumulative release content while the addition of PVP significantly improved both of these features. In release studies through cellophane membrane, the addition of 5 % of penetration enhancer slightly increased the release rate while did not significantly alter cumulative release while the addition of 10 % farnesol notably increased the release rate and total cumulative released content. Release studies through rat skin were in accordance with cellophane membrane studies and the formulation with 10 % farnesol had the most release rate and total cumulative release and these findings confirm the positive effect of penetration enhancers. DSC thermogram showed an amorphous state of the drug in fibres and this was supported by XRD results. The FTIR results confirmed that no chemical interaction between the drug and other formulation components has occurred and no new compounds have been formed. Based on these results, the utilization of DDA-loaded PVP and EC nanofibers in conjunction with a penetration enhancer showed significant potential for application in transdermal patches.

Targeting the Interleukin 23 Pathway in Inflammatory Bowel Disease.

Interleukin (IL) 23, a member of the IL12 family of cytokines, maintains intestinal homeostasis, but is also implicated in the pathogenesis of inflammatory bowel diseases (IBDs). The IL23 receptor is a heterodimer composed of disulfide-linked p19 and p23 subunits. Humanized monoclonal antibodies selectively targeting the p19 subunit of IL23 are poised to become prominent drugs in IBDs. In this review, we discuss the pharmacodynamic and pharmacokinetic properties of the currently available IL23p19 inhibitors and discuss the mechanistic underpinnings of their therapeutic effects, including the mechanism of action, epitope affinity, potency, and downstream signaling. Furthermore, we address available data on the efficacy, safety, and tolerability of IL23-specific p19 inhibitors in the treatment of IBDs and discuss important studies performed in other immune-mediated inflammatory diseases. Finally, we evaluate the potential for combining classes of biological therapies and provide future directions on the development of precision medicine-guided positioning of IL23p19 inhibitors in IBD.

Characterization of macrophages in head and neck squamous cell carcinoma and development of MRG-based risk signature

Macrophages are immune cells in the TME that can not only inhibit angiogenesis, extracellular matrix remodeling, cancer cell proliferation, and metastasis but also mediate the phagocytosis and killing of cancer cells after activation, making them key targets in anti-tumor immunotherapy. However, there is little research on macrophages and their relation to disease prognosis in HNSCC. Initially, we collected scRNA-seq, bulk RNA-seq, and clinical data. Subsequently, we identified macrophages and distinguished MRGs. Using the K-means algorithm, we performed consensus unsupervised clustering. Next, we used ssGSEA analysis to assess immune cell infiltration in MRG clusters. A risk model was established using multivariate Cox analysis. Then, Kaplan–Meier, ROC curves, univariate and multivariate COX analyses, and C-index was used to validate the predictive power of the signature. The TIDE method was applied to assess the response to immunotherapy in patients diagnosed with HNSCC. In addition, drug susceptibility predictions were made for the GDSC database using the calcPhenotype function. We found that 8 MRGs had prognostic potential. Patients in the MRG group A had a higher probability of survival, and MRG clusters A and B had different characteristics. Cluster A had a higher degree of expression and infiltration in MRG, indicating a closer relationship with MRG. The accuracy of the signature was validated using univariate and multivariate Cox analysis, C-index, and nomogram. Immune landscape analysis found that various immune functions were highly expressed in the low-risk group, indicating an improved response to immunotherapy. Finally, drugs with high sensitivity to HNSCC (such as 5-Fluorouracil, Temozolomide, Carmustine, and EPZ5676) were explored and analyze the malignant characteristics of HNSCC. We constructed a prognostic model using multivariate Cox analysis, consisting of 8 MRGs (TGM2, STC1, SH2D3C, PIK3R3, MAP3K8, ITGA5, ARHGAP4, and AQP1). Patients in the low-risk group may have a higher response to immunotherapy. The more prominent drugs for drug selection are 5-fluorouracil, temozolomide and so on. Malignant features associated with HNSCC include angiogenesis, EMT, and the cell cycle. This study has opened up new prospects for the prognosis, prediction, and clinical treatment strategy of HNSCC.

Drug-related side effects and adverse reactions in the treatment of migraine: a bibliometric and visual analysis.

Migraine imposes a substantial global burden, impacting patients and society. Pharmacotherapy, as a primary treatment, entails specific adverse reactions. Emphasizing these reactions is pivotal for improving treatment strategies and enhancing patients' well-being. Thus, we conducted a comprehensive bibliometric and visual analysis of relevant literature. We conducted a comprehensive search on the Science Citation Index Expanded within the Web of Science, restricting the literature for analysis based on criteria such as document type, publication date, and language. Subsequently, we utilized various analytical tools, including VOSviewer, Scimago Graphica, the R package 'bibliometrix', CiteSpace, and Excel programs, for a meticulous examination and systematic organization of data concerning journals, authors, countries/regions, institutions, keywords, and references. By August 31, 2023, the literature was distributed across 379 journals worldwide, authored by 4,235 individuals from 1726 institutions. It featured 2,363 keywords and 38,412 references. 'HEADACHE' led in publication count, with 'SILBERSTEIN S' as the most prolific author. The United States ranked highest in publication volume, with 'UNIV COPENHAGEN' leading among institutions. Our research findings indicate that researchers in the field continue to maintain a focus on the calcitonin gene-related peptide (CGRP) system and explore diverse mechanisms for drug development through the application of novel biotechnological approaches. Furthermore, it is imperative to enhance the assessment of clinical trial outcomes, consistently monitor the efficacy and safety of prominent drugs such as Erenumab and Fremanezumab. There is a need for further evaluation of acute and preventive treatments tailored to different populations and varying types of migraine.

Occurrence of selected pharmaceuticals in wastewater and sludge samples from wastewater treatment plants in Eastern Cape province of South Africa

ABSTRACT The occurrence of pharmaceuticals in various wastewater treatment plants (WWTPs) and their discharge into the surface water are existing global challenges. However, such challenges are more detrimental in developing countries due to the aging infrastructure and its vandalism influenced by poverty, resulting in the illegal breakdown of the WWTPs. This study investigated the presence of efavirenz, ibuprofen, naproxen, sulfamethoxazole, and trimethoprim in WWTPs. Ultrasound-assisted extraction (UAE) followed by solid-phase extraction (SPE) was used to extract these pharmaceuticals in sludge samples, with wastewater extracted with only the latter. This was followed with analysis using a high-performance liquid chromatography-photo-diode array detection system. Recoveries found after spiking the samples with analytes at different concentrations ranged from 56 to 117%. An antibiotic, sulfamethoxazole, was among the prominent drugs in untreated wastewater with its concentration reaching 77 ug L-1. All the analytes were detected in sludge samples, with naproxen having the highest concentration of 13.35 ng g-1. The pharmaceutical with the lowest removal efficiency (2-12%) in WWTPs was efavirenz, while other drugs were fairly removed from wastewater. Overall, the findings of this study indicate the dysfunctionality of selected WWTPs in the Eastern Cape province of South Africa due to the release of high amounts of pharmaceuticals into the surface water which can be detrimental to humans, animals, and aquatic life.

First-principles calculations on monolayer WX2 (X = S, Se) as an effective drug delivery carrier for anti-tuberculosis drugs.

Tuberculosis (TB) remains a major global health concern, necessitating the exploration of novel drug delivery systems to combat the challenges posed by conventional approaches. We investigated the potential of monolayer transition metal dichalcogenides (TMDs) as an innovative platform for efficient and targeted delivery of antituberculosis drugs. Specifically, the electronic and optical properties of prominent TB drugs, isoniazid (INH) and pyrazinamide (PZA), adsorbed on tungsten diselenide (WSe2) and tungsten disulfide (WS2) monolayers were studied using first-principles calculations based on density functional theory (DFT). The investigation revealed that the band gaps of WSe2 and WS2 monolayers remain unaltered upon adsorption of PZA or INH, with negative adsorption energy indicating stable physisorption. We explored different vertical and horizontal configurations, and the horizontal ones were more stable. When INH and PZA drugs were horizontally adsorbed together on WSe2, the most stable configuration was found with an adsorption energy of -2.35 eV. Moreover, the adsorbed drugs could be readily released by light within the visible or near-infrared (NIR) wavelength range. This opened up possibilities for their potential application in photothermal therapy, harnessing the unique properties of these 2D materials. The comprehensive analysis of the band structures and density of states provides valuable insights into how the drug molecules contributed to the conduction and valence bands. The optical responses of anti-TB drugs adsorbed in 2D WSe2 and WS2 were similar to those of pristine 2D WSe2 and WS2. We demonstrated the temperature-dependent release mechanism of our 2D WSe2 and WS2 drug complexes, confirming the feasibility of releasing the discussed anti-tuberculosis drugs by generating heat through photothermal therapy. These findings hold significant promise for developing innovative drug delivery systems that have enhanced efficacy for targeted and low-toxic TB treatment.

FDA와 EMA에서 시판허가된 AAV 기반 유전자치료제의 규제 및 임상시험 설계 측면에서의 사례 연구

Gene therapy, involving the transfer of genetic materials into a patient to alter gene or protein expression, is a promising approach for treating a variety of human diseases. In vivo gene therapy uses gene-based materials to modify target cell genomes. Adeno-Associated Virus (AAV) vectors, known as the safest and the most effective vector to deliver genes of interest into a broad range of cell types, are gaining prominence. Luxturna's the U.S. Food and Drug Administration (FDA) approval marked a turning point for AAV-based gene therapy. Subsequently, Zolgensma and Hemgenix received approval from both the FDA and the European Medicines Agency (EMA), increasing interest in AAV based gene therapies for rare or untreatable diseases. Despite this progress, the regulatory and clinical trial processes for AAV-based gene therapy drugs are underexplored. Our study compares the approval processes of three prominent AAVbased gene therapy drugs: Luxturna, Zolgensma, and Hemgenix. We found that all three received expedited approvals from the FDA and EMA, primarily based on meticulously designed clinical trials demonstrating safety and efficacy. These trials underwent multiple adaptations to meet tight timelines, deviating from traditional regulatory pathways. These findings offer valuable insights for domestic AAV-based gene therapy developers, helping them refine clinical strategies for future innovations. This knowledge would further guide the development and regulation of future AAV-based gene therapies.

Abstract 2912: High-throughput screening and single-cell transcriptomics identify synergies between oncology drugs and natural killer cell immunotherapy

Abstract Background &amp; Objective: Natural killer (NK) cell-based immunotherapies are emerging therapeutic approaches that aim to target malignant cells resistant to conventional treatments and T cell-based immunotherapies. Existing oncology drugs may enhance the anti-cancer function of NK cells, although large-scale high-throughput testing of NK cell-drug combinations has not been previously attempted. Our objective was to evaluate the potential of approved and investigational oncology drugs to synergize with NK cell-based immunotherapy in acute myeloid leukemia (AML), with the aim to discover both potentiating and inhibiting compounds. Methods: A high-throughput drug sensitivity and resistance screen including 528 oncology drugs was combined with expanded NK cells to evaluate their cytotoxicity against luciferase-expressing AML cells (MOLM-14). The most prominent drugs were investigated further with single-cell RNA sequencing to reveal underlying biological mechanisms. Results: Overall, 191 drugs had an inhibitory effect on cytotoxicity, 294 had no effect, and 43 had an enhancing effect. The most notable NK cell cytotoxicity-potentiating drugs were pevonedistat (NEDD8 inhibitor), daporinad (NAMPT inhibitor), and JAK inhibitors. These drugs also induced distinct changes in NK and target cell transcriptional profiles. When combined with NK cells, pevonedistat and daporinad induced an upregulation of HLA-E and CXCL10 in target cells. In addition, MYC and FLT3 proto-oncogenes were downregulated in target cells when combining NK cells with pevonedistat. Moreover, in NK cells, daporinad induced dysregulated expression of genes related to NK cell effector functions such as TYROBP, TXNIP and KLRC1. Treatment with JAK inhibitors downregulated MHC I expression on target cells, providing a putative mechanism for increased NK cell activity. Validation of key hits is ongoing in additional AML cell lines. Conclusion: We discovered novel drugs with both potentiating and inhibiting effects on NK cell cytotoxicity against AML cells in vitro. Our results demonstrate the potential of using a high-throughput framework for studying NK cell-drug interactions against malignant cells, while aiming to improve treatment for AML and other malignancies through combination immunotherapies. Citation Format: Jonas O. Bouhlal, Petra Nygren, Essi Laajala, Aleksandr Ianevski, Jay Klievink, Hanna Lähteenmäki, Khalid Saeed, Dean Lee, Tero Aittokallio, Olli Dufva, Satu Mustjoki. High-throughput screening and single-cell transcriptomics identify synergies between oncology drugs and natural killer cell immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2912.

Interaction of Ibuprofen with Partially Unfolded Bovine Serum Albumin in the Presence of Ionic Micelles and Oligosaccharides at Different λex and pH: A Spectroscopic Analysis.

The interaction between the plasma protein bovine serum albumin (BSA) and the drug ibuprofen (IBU) has been investigated at three different pH values (7.4, 6.5, and 8.0) in the presence of oligosaccharides and surfactants. The interaction analysis of BSA with oligosaccharides and surfactants has also been studied in the absence of the drug ibuprofen. The results obtained give convenient and efficient access to understand the mechanism of binding of ibuprofen to BSA, and the major forces involved are found to be hydrophobic forces, hydrogen bonding and ionic interactions. In addition to that, the formation of inclusion complexes of ibuprofen with oligosaccharides (β-CD and 2-HP-β-CD) has been observed, which has depicted that due to the hydrophobic nature of ibuprofen, it becomes more soluble in the presence of oligosaccharides, but due to the larger size of the inclusion complexes, these could not be able to access the hydrophobic pocket of BSA where tryptophan-212 (Trp-212) resides. The binding interaction between BSA and ibuprofen is observed in the presence of surfactants (SDS and CTAB), which partially unfold the protein. Non-radiative fluorescence resonance energy transfer (FRET) from Trp and Tyr residues of BSA in the presence of an anionic surfactant SDS to ibuprofen has depicted that there is a possibility of drug binding even in the partially unfolded state of BSA protein. Furthermore, the distance between the protein and the drug has been calculated from the FRET efficiency, which gives a comprehensive overview of ibuprofen binding to BSA even in its partially denatured state. The hydrophobic drug binding to the partially unfolded serum albumin protein (BSA) supports the "necklace and bead structures" model and opens up a new direction of drug loading and delivery system, which will have critical therapeutic applications in the efficient delivery of pharmacologically prominent drugs.

Bismuth nanoparticles against microbial infections.

The destructive effect of infectious diseases on human life and the emergence of antibiotic-resistant strains highlight the importance of developing new and appropriate treatment strategies, one of which is the use of metals astherapeutic agents. Bismuth nanoparticles are an example of prominent metal-containing drugs. The therapeutic effects of bismuth-based drugs in the treatment of wounds have been proven. Various laboratory studies have confirmed the antimicrobial effects of bismuth nanoparticles, including the clinical treatment of ulcers caused by Helicobacter pylori. Therefore, considering the performance of this nanoparticle and its potent effect on infectious agents and its therapeutic dimensions, the present study fully investigated the properties and performance of this metal-based nanoparticle.

Crystal structures of Schistosoma mansoni histone deacetylase 8 reveal a novel binding site for allosteric inhibitors

Parasitic diseases cause significant global morbidity and mortality particularly in the poorest regions of the world. Schistosomiasis, one of the most widespread neglected tropical diseases, affects more than 200 million people worldwide. Histone deacetylase (HDAC) inhibitors are prominent epigenetic drugs that are being investigated in the treatment of several diseases, including cancers and parasitic diseases. Schistosoma mansoni HDAC8 (SmHDAC8) is highly expressed in all life cycle stages of the parasite, and selective inhibition is required in order to avoid undesirable off-target effects in the host. Herein, by X-ray crystal structures of SmHDAC8-inhibitor complexes, biochemical and phenotypic studies, we found two schistosomicidal spiroindoline derivatives binding a novel site, next to Trp198, on the enzyme surface. We determined that by acting on this site, either by mutation of the Trp198 or by compound binding, a decrease in the activity of the enzyme is achieved. Remarkably, this allosteric site differs from the human counterpart; rather, it is conserved in all Schistosoma species, as well as Rhabidoptera and Trematoda classes, thus paving the way for the design of HDAC8-selective allosteric inhibitors with improved properties.

Structural Modeling of Drosophila melanogaster Gut Cytochrome P450s and Docking Comparison of Fruit Fly Gut and Human Cytochrome P450s.

Drosophila melanogaster is a prominent organism in developmental biology research and in studies related to pathophysiological conditions like cancer and Alzheimer's disease. The fruit fly gut contains several cytochrome P450s (CYP450s), which have central roles in Drosophila development and in the normal physiology of the gut. Since the crystal structures of these proteins have not been deciphered yet, we modeled the structure of 29 different D. melanogaster gut CYP450s using Prime (Schrödinger). The sequences of chosen D. melanogaster gut CYP450s were compared with that of their human counterparts. The common gut (and liver) microsomal CYP450s in humans were chosen for structural comparison to find the homology and identity % of D. melanogaster CYPs with that of their human counterparts. The modeled structures were validated using PROCHECK and the best fit models were used for docking several known human pharmacological agents/drugs to the modeled D. melanogaster gut CYP450s. Based on the binding affinities (ΔG values) of the selected drug molecules with the modeled fly gut CYPs, the plausible differences in metabolism of the prominent drugs in humans and flies were projected. The gut is involved in the absorption of oral drugs/pharmacological agents, and hence, upregulation of intestinal CYP450 and their reactions with endobiotics and xenobiotics is envisaged. The insights gleaned from this work can validate D. melanogaster as a model organism for studying intestinal drug metabolism, particularly in the context of a) toxicology of pharmacological agents to the gut cells and b) how gut P450 metabolites/products can influence gut homeostasis. This work can help establish a platform for further in vitro investigations on how intestinal CYP450 metabolism can influence gut health. The data from this work can be used for further in silico studies and this work can serve as a platform for future in vitro investigations on intestinal CYP450-mediated metabolism of endo- and xeno-biotics in D. melanogaster.

Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents.

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.

Review of Pharmacotherapy Trialed for Management of the Coronavirus Disease-19.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been substantial progress in the pharmacologic treatment and supportive care of patients hospitalized with active COVID-19 infections. To date there have been numerous medications trialed for COVID-19 management. In this review, our objective is to provide a comprehensive review of the primary literature and clinical applications surrounding some of the prominent drugs and medication classes that have been utilized in those suffering from COVID-19 infections. The medications reviewed in this article include: hydroxychloroquine, remdesivir, azithromycin, dexamethasone, melatonin, tocilizumab, ascorbic acid, and zinc. The medication classes reviewed include: anticoagulation, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, convalescent plasma, non-steroidal anti-inflammatory drugs, human recombinant soluble ACE2, and the BNT162b2 mRNA COVID-19 vaccine.

Novel therapeutics for the treatment of hypertension and its associated complications: peptide- and nonpeptide-based strategies.

The renin-angiotensin-aldosterone system (RAAS) is responsible for maintaining blood pressure and vascular tone. Modulation of the RAAS, therefore, interferes with essential cellular processes and leads to high blood pressure, oxidative stress, inflammation, fibrosis, and hypertrophy. Consequently, these conditions cause fatal cardiovascular and renal complications. Thus, the primary purpose of hypertension treatment is to diminish or inhibit overactivated RAAS. Currently available RAAS inhibitors have proven effective in reducing blood pressure; however, beyond hypertension, they have failed to treat end-target organ injury. In addition, RAAS inhibitors have some intolerable adverse effects, such as hyperkalemia and hypotension. These gaps in the available treatment for hypertension require further investigation of the development of safe and effective therapies. Current research is focused on the combination of existing and novel treatments that neutralize the angiotensin II type I (AT1) receptor-mediated action of the angiotensin II peptide. Preclinical studies of peptide- and nonpeptide-based therapeutic agents demonstrate their conspicuous impact on the treatment of cardiovascular diseases in animal models. In this review, we will discuss novel therapeutic agents being developed as RAAS inhibitors that show prominent effects in both preclinical and clinical studies. In addition, we will also highlight the need for improvement in the efficacy of existing drugs in the absence of new prominent antihypertensive drugs.

Effect of Shadbindu Taila and Haridra Khanda in Pratishyaya (Allergic Rhinitis)

Allergic rhinitis (AR) is an immune response of the nasal mucosa to airborne allergens and involves nasal congestion, watery nasal discharge, itching of the nose, and sneezing. Ayurveda describes Pratishyaya as one of the most important diseases among the 31 Nasarogas. Acharya Sushruta clearly mentioned that Pratishyaya is the condition in which vata kapha dusti was observed. Haridra Khanda is one of the prominent anti allergic drugs mentioned in ayurveda. Pratimarsha nasya has significant role in the prevention of urdhvajatrugata rogas. Ancient acharya has told to try shadbindu taila and Haridra khanda both locally and systematically in the management of pratishyaya. Here 30 patients were selected open randomly in shalakya opd of ayurveda campus kirtipur. They were given pratimarsha nasya with sadhbindu taila and internally haridra khanda for 30 days. The vital sign and symptom of pratishyaya like nasa srava, nasa kandu, kshavatu, nasa kandu and shira shula were studied before and after the treatment. The result of the study indicated that the combined therapy of internally Haridra Khanda and external pratimarsha narsha with sadbindu tail has given significant result in the treatment of Allergic Rhinitis (Pratishyaya).

In vitro anti-inflammatory activity of silymarin/hydroxyapatite/chitosan nanocomposites and its cytotoxic effect using brine shrimp lethality assay.

Silymarin, a bioactive compound, is one of the most prominent drugs used in liver diseases. Chitosan and hydroxyapatite (HAP) are the major materials used employed in many biomedical processes like drug delivery, osteointegration, etc. The nanoparticles and nanocomposites are advanced materials with many biomedical applications in diagnosis and therapeutics. In this study, HAP and chitosan were used as a polymeric material, silymarin as a bioactive compound, and other nanoparticle based combinations. The prepared individual materials and nanocomposites were used for the anti-inflammatory activity and brine shrimp lethality assay. The results clearly show that the nanocomposites are good anti-inflammatory agents with lower toxicity.

Strategic responses and disclosures in a sporting drugs scandal: the case of the Essendon Football Club

This case utilises Oliver's (1991) framework of strategic responses to institutional processes to provide insights into the actions of an Australian football club faced with a prominent drugs scand...